Summary

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different
ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Vorinostat may help temozolomide work better by making tumor cells more sensitive
to the drug.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when
given together with temozolomide in treating young patients with relapsed or refractory
primary brain tumors or spinal cord tumors.

- To define and describe the toxicities of this regimen in these patients.

Secondary

- To preliminarily define the antitumor activity of this regimen within the confines of a
phase I study.

- To characterize the pharmacokinetic parameters of vorinostat in these patients.

- To determine whether acetylated histones in peripheral blood mononuclear cells can be
identified as a surrogate marker of the biologic effect of vorinostat at various
treatment doses.

- To assess the feasibility of collecting and analyzing serum DNA for methylation of the
MGMT promoter and describe the relationship between promoter methylation and clinical
responses within the confines of this phase I study.

OUTLINE: This is a multicenter, dose-escalation study of vorinostat.

Patients receive oral vorinostat and oral temozolomide once daily on days 1-5. Courses
repeat every 28 days for up to 13 courses in the absence of disease progression or
unacceptable toxicity.

Hematopoietic stem cells (HSCs) are rare cells, with the mouse bone marrow containing only ~25,000 phenotypic long term repopulating HSCs. A Western blotting protocol was optimized and suitable for th...

New findings identified the MORC1 gene as a link between early life stress and major depression. In this study, MORC1 methylation was investigated in 60 healthy human adults (30 women, 30 men) between...

Both β-value and M-value have been used as metrics to measure methylation levels. The M-value is more statistically valid for the differential analysis of methylation levels. However, the β-value is...

Although methylation of the O-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best fo...

Medical and Biotech [MESH] Definitions

Blotting, Southwestern

A method that is used to detect DNA-protein interactions. Proteins are separated by electrophoresis and blotted onto a nitrocellulose membrane similar to Western blotting (BLOTTING, WESTERN) but the proteins are identified when they bind labeled DNA PROBES (as with Southern blotting (BLOTTING, SOUTHERN)) instead of antibodies.

Blotting, Far-western

A method that is derived from western blotting (BLOTTING, WESTERN) and is used to detect protein-protein interactions. The blotted proteins are probed with a non-antibody protein which can then be tagged with a labeled antibody.

Blotting, Western

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Blotting, Northern

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Blotting, Southern

A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

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